Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine.

Yusuke Wataya, Tomoharu Naito, Akira Sato, Akiko Hiramoto, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Hye Sook Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (3'-Ethynylcytidine; ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. We have investigated the cancer-cell death induced by ECyd, focusing on its molecular mechanisms. In ECyd-treated cells, RNase L is activated and involved in c-jun NH(2)-terminal kinase (JNK) phosphorylation, followed by induction of mitochondria-dependent apoptosis. The mechanism of JNK phophorylation by RNase L was unknown. To investigate the mechanism, we performed the identification of RNase L-binding partners by proteomic approach using co-immunoprecipitation and mass spectrometry. We found that RNase L was associated with a protein (we named it Protein-190). At the same time, we observed that Protein-190 was amply phosphorylated. Furthermore, the participation of Protein-190 in the ECyd-induced apoptosis was supported by a knockdown experiment using small interfering RNA (siRNA). Thus, the number of ECyd-induced apoptotic cells was drastically decreased when Protein-190 was knocked-down. These results indicated Protein-190 as a regulator in apoptosis, and provide the possibility for a new clinical target in cancer chemotherapy.

Original languageEnglish
Pages (from-to)291-292
Number of pages2
JournalNucleic acids symposium series (2004)
Issue number53
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Medicine(all)

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